Urease (urea amidohydrolase EC 3.3.1.5) catalyzes the hydrolysis of urea to form ammonia and carbamate. The later compound spontaneously hydrolyzes at physiological pH to form carbonic acid and a second molecule of ammonia.
Urea is a major nitrogenous waste product of biological actions which is rapidly metabolized by microbial activities. The enzyme is widely distributed in a variety of bacteria, fungi and plants, thus playing an important role in the circulation of nitrogen in nature as they catalyzes the urea degradation to supply these organisms with a source of nitrogen for growth.
In agriculture, high urease activity causes significant environmental and economic problems by releasing abnormally large amounts of ammonia into the atmosphere during urea fertilization (the most widely used fertilizer in the world). This further induces plant damage primarily by depriving plants from their essential nutrients and secondly through ammonia toxicity and carbon dioxide release that increases the pH of the soil. Many microorganisms use this enzyme to provide a source of nitrogen for growth, as it plays an important role in plant nitrogen metabolism during the germination process. The presence of urease activity in soils is exploited in the widespread agricultural practices for enhancing crop yields.
Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. Urease is known to be one of the major causes of pathologies induced by Helicobacter pylori, thus allow them to survive at low pH of the stomach and, therefore, play an important role in the pathogenesis of gastric and peptic ulcer. Proteus mirabilis and Yersinia enterocolitica are responsible for urolithiasis and involve in the development of acute pyelonephritis and infection-induced reactive arthritis, respectively. The obvious remedy for treating bacterial infection with antimicrobials has often proven futile, and only a few combination regiments have reached clinical practice. Thus the need for alternative or novel treatment is evident.
The discovery of potent and safe urease inhibitors have been a very important area of pharmaceutical research due to the involvement of ureases in different pathological conditions.
Thiazole derivatives have attracted major interest of bioorganic chemists due to their antimicrobial and other biological activities. They exhibit prominent antiviral, anti-mycobacterial and anti-proliferative activities. Thiazole derivatives have been found to have analgesic, anti-inflammatory, anti-nociceptive, and selective acetyl CoA carboxylase-2 inhibitory activity.